A 4-week double-blind, randomized, placebo-controlled, phase II study evaluating the effects of oral pamapimod 150 mg with pioglitazone 10 mg daily on COVID-19 evolution and recovery in non-hospitalized patients infected with SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kinarus AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

25 Aug 2022 → 24 Apr 2025

Decision date (initial)

2022-08-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Kinarus AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Number of days alive with no score > 1 in each of the symptoms and a maximum of 3 points in the total score, measured from inclusion to day 28

Secondary objectives 7

1. Time to clinical recovery, based on patient-reported daily evaluation of symptoms (Table 1), and defined as the numberof days from start of administration of the investigational agent to the first of two consecutive days when any symptoms scoredas2 or 3 at study entry are scored as 0-1 AND any symptoms scored as 0-1at study entry are scored as 0
2. All-cause unplanned COVID-19 related hospital admission for at least 24 hours or death by day 28
3. Total sum of daily scores of symptoms from inclusion to day 28
4. Proportion of patients with full recovery at day 14 and day 28(no more than 3 items scoring > 1)
5. Safety and tolerability of pamapimod used in combination with pioglitazone (AEs, SAEs)
6. CRP/hsCRP value at day 14
7. Number of family members (same household) testing positive by PCR test 2 to 10 days after inclusion

Conditions and MedDRA coding

COVID-19

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of symptomatic COVID-19 of less than 5 days’ duration, with at least 1 point in at least 4 items of the symptom evaluation table, and at least 2 points in at least 2 items, OR a minimum total score of 6 points (Table 1)
2. Diagnosis of COVID-19 confirmed in the last 48 hours by a positive test for SARS-CoV-2 RNA by RT PCR or a rapid validated antigen test (excluding self-test), in a specimen from the upper respiratory tract, the saliva (antigen test), the lower respiratory tract or an expectorated sputum
3. No indication that the patient will be hospitalized in the next 48 hours for COVID-19 related reasons
4. Adult male or female patients aged ≥ 18 years
5. Females must have a negative pregnancy test or must be post-menopausal
6. Able to understand and willing to sign an IRB/IEC approved written informed consent document.
7. Able to understand and be available for daily phone calls to evaluate symptoms.

Exclusion criteria 11

1. Patients with an indication for hospitalization (e.g. SpO2 <92%)
2. Patients participating in another clinical trial with a new investigational drug or investigational non-drug treatment
3. Known allergy or intolerance to pamapimod or any other ingredient of the IMP or another P38 inhibitor
4. Known allergy or intolerance of clinical relevance to pioglitazone or any other ingredient of the IMP.
5. Patients where oral administration of pioglitazone is contraindicated (i.e. cardiac failure or history of cardiac failure (NYHA stages I to IV),with hepatic impairment, diabetic ketoacidosis, current bladder cancer or a history of bladder cancer, uninvestigated macroscopic haematuria
6. Any use of CYP450 2C8 inducers (e.g. rifampicin)
7. Known or suspected active viral (including HIV, hepatitis B, hepatitisC), bacterial, mycobacterial or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected.
8. Pregnant or breastfeeding women
9. Any uncontrolled concurrent illness that would put the patient at a greater risk or limit compliance with the study requirements as determined at the discretion of the investigator
10. Liver enzyme elevation more than 3x above normal in the last 4weeks or at inclusion
11. Patients who are detained or committed to an institution by a lawcourt or by legal authorities (subject is vulnerable, such as deprived of freedom)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of days alive with no score > 1 in each of the symptoms and a maximum of 3 points in the total score, measured from inclusion to day 28

Secondary endpoints 8

1. Time to recovery, based on patient-reported daily evaluation of symptoms
2. All-cause unplanned hospital admission for at least 24 hours or death by day 28
3. Total sum of daily score of symptoms from inclusion to day 28
4. Number of days with no symptoms scoring > 1 from inclusion today 14 and day 28
5. Proportion of patients with full recovery at day 14 and day 28 (no more than 3 items scoring > 1)
6. Inflammatory markers values at day 14 (hsCRP)
7. Safety and tolerability of pamapimod used in combination with pioglitazone (AEs, SAEs)
8. Number of family members (same household) testing positive by rtPCR test within 2 to 10 days after inclusion

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kinarus AG

Sponsor organisation

Kinarus AG

Address

Technologiepark, Hochbergerstrasse 60c Hochbergerstrasse 60c

City

Basel

Postcode

4057

Country

Switzerland

Scientific contact point

Organisation

Kinarus AG

Contact name

Thierry Fumeaux

Public contact point

Organisation

Kinarus AG

Contact name

Claudia Berger

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Application history

2 submissions — initial application plus substantial / non-substantial modifications